Neurogenetics Reference Lab · Teaching Example
- Panel
- Epilepsy / Encephalopathy Panel (385 genes)
- Report ID
- TEACH-0010
- Indication
- Infantile-onset focal motor seizures, developmental delay.
- Specimen
- Peripheral blood, EDTA · Received 2026-04-08
- Reported
- 2026-04-22
- Methodology
- Targeted capture NGS, mean depth 230×. SpliceAI in silico splice prediction reported routinely. Trio analysis.
Patient (anonymized teaching example)
Age 11 months · Male · European ancestry
Clinical: Onset at 5 months with focal motor seizures. Developmental plateau. Normal MRI. No family history.
Reportable Variants
| Gene | Variant | Zygosity | Condition (Mode) | Origin | Classification |
|---|---|---|---|---|---|
Interpretation
A heterozygous SCN8A variant c.2937A>G (p.Lys979=) was identified, occurring de novo (trio-confirmed). Although the variant is (synonymous codon change), it lies at the and is predicted to disrupt the splice donor site (). The variant is absent from gnomAD and the predicted effect would be exon skipping or use of a cryptic splice site, producing an aberrant transcript. SCN8A-related encephalopathy is typically caused by missense variants; the disease consequences of a putative splice-disrupting variant are uncertain. Classification: VUS. are recommended to confirm the splicing effect, which would substantially clarify pathogenicity.
Recommendations
- •RNA studies (RT-PCR from a fresh sample, or blood-based RNA-seq) to confirm or refute the predicted splice disruption. This is the highest-yield reclassification step.
- •Continue seizure management based on clinical picture; do not alter therapy on the basis of a VUS.
- •Genetic counseling for the family; recurrence risk <1% if de novo origin maintained.
- •Reclassification reassessment in 1–2 years.